Composition for transdermal and dermal administration of interferon-α

Abstract

A composition for transdermal and dermal administration of interferon-alpha is described. The composition is comprised of lipid vesicles including a fatty acylated amino acid and an oil-in-water emulsion. Interferon-alpha is entrapped in the vesicles.

It is claimed:  
     
       1. An interferon-α composition, comprising 
       biphasic lipid vesicles comprised of (i) a lipid bilayer comprising a phospholipid and a fatty acylated amino acid; (ii) an oil-in-water emulsion entrapped in the biphasic lipid vesicles, said oil-in-water emulsion being stabilized by a surfactant; and (iii) interferon-α entrapped in said vesicles;  
       said fatty acylated amino acid being represented by the formula:                    
       wherein R 1  is an acyl group having from 1-20 carbons, R 2  is hydrogen or an alkyl group, and R 3  corresponds to a modified or unmodified R group of an amino acid selected from the group consisting of glycine, alanine, serine, aspartic acid, arginine, valine, threonine, glutamic acid, leucine, cysteine, histidine, lsoleucine, tyrosine, asparagine, methionine, proline, tryptophan, phenylalanine, and glutamine;  
       wherein said composition when applied to the skin of a subject being effective to administer a therapeutically effective amount of interferon-α.  
     
     
       2. The composition of  claim 1 , wherein said acylated amino acid is for dermal administration of interferon-α. 
     
     
       3. The composition of  claim 1 , wherein said acylated amino acid is for transdermal administration of interferon-α. 
     
     
       4. The composition of  claim 1 , wherein said R group of amino acid is the R group of serine or threonine. 
     
     
       5. The composition of  claim 1 , wherein said oil-in-water emulsion further comprises a fatty alcohol. 
     
     
       6. The composition of  claim 5 , wherein said fatty alcohol is has between about 8-24 carbon atoms. 
     
     
       7. The composition of  claim 1 , wherein said oil-in-water emulsion further comprises a triglyceride. 
     
     
       8. The composition of  claim 7 , wherein said triglyceride is a pharmaceutically acceptable oil. 
     
     
       9. The composition of  claim 8 , wherein said synthetic oil is selected from the group consisting of canola oil and olive oil. 
     
     
       10. The composition of  claim 1 , wherein said oil-in-water emulsion is further comprised of a fatty glyceride dispersed in the water phase and stabilized by said surfactant. 
     
     
       11. The composition of  claim 10 , wherein said fatty glyceride is glycerol monostearate. 
     
     
       12. The composition of  claim 1 , wherein said lipid bilayer is further comprised of a sterol. 
     
     
       13. An interferon-α composition, comprising 
       biphasic lipid vesicles comprised of (i) a lipid bilayer comprised of a phospholipid and an acylated amino acid represented by the formula:                    
       wherein R 1  is an acyl group having from 1-20 carbons, R 2  is hydrogen or an alkyl group, and R 3  corresponds to a modified or unmodified R group of an amino acid selected from the group consisting of glycine, alanine, serine, aspartic acid, arginine, valine, threonine, glutamic acid, leucine, cysteine, histidine, isoleucine, tyrosine, asparagine, methionine, proline, tryptophan, phenylalanine, and glutamine; (ii) an oil-in-water emulsion entrapped in the biphasic lipid vesicles, said oil-in-water emulsion comprised of a triglyceride that is dispersed in a water phase containing a fatty alcohol and that is stabilized by a surfactant; and (iii) interferon-α entrapped in said vesicles;  
       wherein said composition when applied to the skin of a subject being effective to administer a therapeutically effective amount of interferon-α.  
     
     
       14. The composition of  claim 13 , wherein said acylated amino acid is for dermal administration of interferon-α. 
     
     
       15. The composition of  claim 13 , wherein said acylated amino acid is for transdermal administration of interferon-α. 
     
     
       16. The composition of  claim 13 , wherein said R group of an amino acid is the R group of serine or threonine. 
     
     
       17. The composition of  claim 13 , wherein said lipid bilayer further includes cholesterol. 
     
     
       18. The composition of  claim 13 , wherein said triglyceride is canola oil. 
     
     
       19. The composition of  claim 13 , wherein said surfactant is a cationic phospholipid. 
     
     
       20. The composition of  claim 13 , wherein said lipid bilayer further includes cholesterol. 
     
     
       21. The composition of  claim 13 , wherein said triglyceride is a pharmaceutically acceptable oil. 
     
     
       22. The composition of  claim 21 , wherein said oil is selected from the group consisting of canola oil and olive oil. 
     
     
       23. The composition of  claim 13 , wherein fatty alcohol has between about 2-24 carbon atoms. 
     
     
       24. An interferon-α composition, comprising 
       biphasic lipid vesicles comprised of (i) a lipid bilayer comprising a phospholipid and a fatty acylated amino acid; (ii) an oil-in-water emulsion entrapped in the biphasic lipid vesicles, said oil-in-water emulsion being stabilized by a surfactant; and (iii) interferon-α entrapped in said vesicles;  
       said fatty acylated amino acid being represented by the formula:                    
        wherein  
       R 1  is hydrogen or an acyl group having less than 16 carbons and R 2  is hydrogen or an alkyl group, but when R 1  is hydrogen, R 2  is an alkyl group, and R 3  corresponds to a modified or unmodified lysine R group;  
       wherein said composition when applied to a subject being effective to administer a therapeutically effective amount of interferon-α.  
     
     
       25. The composition of  claim 24 , wherein said acylated amino acid is for dermal administration of interferon-α. 
     
     
       26. The composition of  claim 24 , wherein said acylated amino acid is for transdermal administration of interferon-α. 
     
     
       27. The composition of  claim 24 , wherein said oil-in-water emulsion further comprises a fatty alcohol. 
     
     
       28. The composition of  claim 27 , wherein said fatty alcohol is has between about 8-24 carbon atoms. 
     
     
       29. The composition of  claim 24 , wherein said oil-in-water emulsion further comprises a triglyceride. 
     
     
       30. The composition of  claim 29 , wherein said triglyceride is a pharmaceutically acceptable oil. 
     
     
       31. The composition of  claim 30 , wherein said oil is selected from the group consisting of canola oil and olive oil. 
     
     
       32. The composition of  claim 24 , wherein said oil-in-water emulsion is further comprised of a fatty glyceride dispersed in the water phase and stabilized by said surfactant. 
     
     
       33. The composition of  claim 32 , wherein said fatty glyceride is glycerol monostearate. 
     
     
       34. The composition of  claim 24 , wherein said lipid bilayer is further comprised of a sterol. 
     
     
       35. An interferon-α composition, comprising biphasic lipid vesicles comprised of (i) a lipid bilayer comprised of a phospholipid and an acylated amino acid represented by the formula:                    
       wherein R 1  is hydrogen or an acyl group having less than 16 carbons and R 2  is hydrogen or an alkyl group, but when R 1  is hydrogen, R 2  is an alkyl group, and R 3  corresponds to a modified or unmodified lysine R group; (ii) an oil-in-water emulsion entrapped in the biphasic lipid vesicles, said oil-in-water emulsion comprised of a triglyceride that is dispersed in a water phase containing a fatty alcohol and that is stabilized by a surfactant; and (iii) interferon-α entrapped in said vesicles; 
       wherein said composition when applied to a subject being effective to administer a therapeutically effective amount of interferon-α.  
     
     
       36. The composition of  claim 35 , wherein said acylated amino acid is for dermal administration of interferon-α. 
     
     
       37. The composition of  claim 35 , wherein said acylated amino acid is for transdermal administration of interferon-α. 
     
     
       38. The composition of  claim 35 , wherein said lipid bilayer further includes cholesterol. 
     
     
       39. The composition of  claim 35 , wherein said triglyceride is canola oil. 
     
     
       40. The composition of  claim 35 , wherein said surfactant is a cationic phospholipid. 
     
     
       41. The composition of  claim 35 , wherein said lipid bilayer further includes cholesterol. 
     
     
       42. The composition of  claim 35 , wherein said triglyceride is a pharmaceutically acceptable oil. 
     
     
       43. The composition of  claim 35 , wherein said oil is selected from the group consisting of canola oil and olive oil. 
     
     
       44. The composition of  claim 35 , wherein fatty alcohol has between about 2-24 carbon atoms. 
     
     
       45. The composition of  claim 4 , wherein said acylated amino acid is selected from the group consisting of N-capryloyl-L-threonine methyl ester, N-eicosanoyl-L-serine, and N-eicosanoyl threonine. 
     
     
       46. The composition of  claim 16 , wherein said acylated amino acid is selected from the group consisting of N-capryloyl-L-threonine methyl ester, N-eicosanoyl-L-serine, and N-eicosanoyl threonine.